{"doi":"10.3233/jpd-230129","title":"Alpha-Synuclein Pre-Formed Fibrils Injected into Prefrontal Cortex Primarily Spread to Cortical and Subcortical Structures","abstract":"BACKGROUND: Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) are characterized by diffuse spread of alpha-synuclein (α-syn) throughout the brain. Patients with PDD and DLB have a neuropsychological pattern of deficits that include executive dysfunction, such as abnormalities in planning, timing, working memory, and behavioral flexibility. The prefrontal cortex (PFC) plays a major role in normal executive function and often develops α-syn aggregates in DLB and PDD. OBJECTIVE: To investigate the long-term behavioral and cognitive consequences of α-syn pathology in the cortex and characterize pathological spread of α-syn. METHODS: We injected human α-syn pre-formed fibrils into the PFC of wild-type male mice. We then assessed the behavioral and cognitive effects between 12- and 21-months post-injection and characterized the spread of pathological α-syn in cortical, subcortical, and brainstem regions. RESULTS: We report that PFC PFFs: 1) induced α-syn aggregation in multiple cortical and subcortical regions with sparse aggregation in midbrain and brainstem nuclei; 2) did not affect interval timing or spatial learning acquisition but did mildly alter behavioral flexibility as measured by intraday reversal learning; and 3) increased open field exploration. CONCLUSIONS: This model of cortical-dominant pathology aids in our understanding of how local α-syn aggregation might impact some symptoms in PDD and DLB.","journal":"Journal of Parkinson s Disease","year":2023,"id":332987,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9594,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1060207,"name":"Gemma Kerr","orcid":null,"position":1,"is_corresponding":false},{"id":336693,"name":"Ramasamy Thangavel","orcid":"0000-0001-5006-7914","position":2,"is_corresponding":false},{"id":733766,"name":"Mackenzie M. Conlon","orcid":"0000-0003-2126-3064","position":3,"is_corresponding":false},{"id":257537,"name":"Serena B. Gumusoglu","orcid":"0000-0002-2098-388X","position":4,"is_corresponding":false},{"id":291042,"name":"Kalpana Gupta","orcid":"0000-0002-6766-3576","position":5,"is_corresponding":false},{"id":733763,"name":"Hisham Abdelmotilib","orcid":"0000-0001-8346-3366","position":6,"is_corresponding":false},{"id":1060208,"name":"Oday Halhouli","orcid":null,"position":7,"is_corresponding":false},{"id":296031,"name":"Qiang Zhang","orcid":"0000-0002-4746-0392","position":8,"is_corresponding":false},{"id":291007,"name":"Joel C. Geerling","orcid":"0000-0001-9956-4006","position":9,"is_corresponding":false},{"id":98533,"name":"Nandakumar S. Narayanan","orcid":"0000-0002-0427-0003","position":10,"is_corresponding":false},{"id":296032,"name":"Georgina M. Aldridge","orcid":"0000-0002-8025-1189","position":11,"is_corresponding":false},{"id":44830,"name":"Matthew A. Weber","orcid":"0000-0003-0488-1792","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-19T01:09:35.125543Z","pmid":"38189765","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}